Degenerative disorders of the sensory retina can have a devastating impact on quality of life with significant socioeconomic consequences. About 1 million people in the United States alone suffer profound vision loss, with another 2.4 million having some degree of visual impairment. As the U.S. population continues to age, it is likely that the total number of affected individuals will increase, possibly by up to 50% by 2020, especially given the dramatic rise in type II diabetes. Attempts to treat these disorders by slowing the rate of degeneration and reversing the resultant loss of vision have included genetic, pharmacological, surgical, and cellular interventions, such as the use of stem cell therapy. While these treatments offer some promise, they also face numerous challenges that have blocked some of the most promising therapies from general clinical acceptance. One exception if anti-vascular endothelial growth factor (VEGF) therapy, however, it only treats one form of late stage age-related macular degeneration, and many patients still are unable to attain driving-level vision. Some forms of neural blindness, such as retinitis pigmentosa and Stargardt disease, cannot currently be treated by any available means.
A number of projects have been undertaken to develop a retinal implant capable of restoring vision to patients suffering retinal diseases. Retinal, conical and optic nerve visual prostheses use microfabricated electronic components that can be surgically implanted to replace the lost photoreceptor (PR) neurons. Two primary sites of stimulation and surgical implantation have been explored: subretinally, with the device implanted in the space where photoreceptors used to be, or epiretinally, directly stimulating the ganglion cells. Retinal prostheses do not generally have the potentially irreversible side effects of some molecular and biological therapeutic approaches, which can include formation of tumors. In addition, with well-established surgical methods for implanting retinal prostheses, implants can be removed if needed. Nonetheless, in spite of decades of research, visual prostheses have not advanced beyond early clinical trials and have not yet produced a level of vision that has been demonstrated to improve the ability of patients to perform visual tasks related to daily activities. Existing devices are subject to serious limitations in their ability to reach appropriate electrode densities and stimulation resolutions. These limitations are largely due to the dependence on microelectrode technologies, which goes beyond the size of the microelectrodes themselves, because each electrode must be individually addressed and interconnected so it can receive injected current from the photosensing part of the prosthesis, which is separate from the microelectrode array itself. Microelectrode devices must first detect light, possibly with an external camera or microphotodiode array then determine the amount of current to be injected into each microelectrode using on-board processing. This circuitry consumes considerable space, so while the photosensing element, e.g., CCD camera, may have extremely high resolution, there is a physical limitation to the density of stimulation and, hence, the overall resolution of the device will be limited.
One example of microelectrode technology is the FDA-approved ARGUS® II (Second Sight Medical Products. Inc. (Sylmar, Calif.)) epiretinal device, which exhibits a best acuity of 20/1260 with 60 electrodes. The number of electrodes that would be needed to yield significant levels of visual acuity has been estimated to be within the range of 256 to 625 electrodes, which theoretically might yield best visual acuity of 20/240 and 20/30, respectively. The high density of ganglion cells in the retina suggests that a greater number of stimulating electrodes could be implanted in a given area, however, the number of electrodes required depends on the ability of the materials to safely transmit charge and on the proximity of the target tissue to those electrodes.
Neural and muscular stimulators used in implants and prosthetic devices such as retinal implants, cochlear implants, and cardiac pacemakers, among others, deliver electrical current, usually from a conventional current source, to tissue. Many of these devices rely on wireless power transmission from an external power supply, requiring complex circuitry for power telemetry, data telemetry, power management, clock recovery, digital control, and driving stimulation pulse. The current sources rely on a significant voltage drop across a transistor to maintain a constant current, and draw current from large DC voltage supplies, consuming relatively high levels of power for each electrode. The required power generated during stimulation is generates heat which results in damage to the surrounding tissue. Tissue such as the retina is particularly sensitive to temperature-induced damage. As described above, it is estimated that in order to obtain the desired resolution, the number of electrodes in a retinal implant will be in the hundreds to thousands. In addition to increasing heat dissipation of the stimulator, higher power consumption also exposes the surrounding tissue to larger magnetic fields due to the demand for high power transmission from the external battery power supply. Several factors that determine power consumption may be beyond the control of the designer, including the threshold for perception or function, electrode size or material.
For many reasons, including the challenges described above, the barriers to restoring vision to the blind are significant. In addition to biomaterial issues such as toxicity, tissue encapsulation and cellular/immune responses that might be triggered by foreign materials, an electrical prosthesis must also provide long-term stability of the metal electrodes while minimizing any tissue damage that occurs as a result of the electrical stimulation. Induced tissue damage will reduce the excitability of the tissue and limit the potential for vision restoration. The potential biocompatibility and long-term functional stability of a retinal prosthesis are further complicated by ongoing anatomical and physiological changes that inevitably occur within the retina in patients with retinitis pigmentosa, the primary disease that has been targeted by early visual prosthetic implantations.
A field that shows promise in overcoming the limitations of existing microelectrode-based implants is nanotechnology. As is known in the art, when particles of materials have dimensions of around 1-10 μm, the particles' properties and behavior are dominated by quantum effects. As used herein, a “nanomaterial” is a material in which quantum effects rule the behavior and properties of particles. When particle size is in the nanoscale range, properties such as melting point, fluorescence, electrical conductivity, magnetic permeability, and chemical reactivity change as a function of the size of the particle. As used herein, a “nanodevice” is a device formed from nanomaterials. Nanodevices and nanomaterials can interact with biological systems at fundamental molecular levels. By taking advantage of this unique molecular specificity, these nanotechnologies can stimulate, respond to and interact with target cells and tissues in controlled ways to induce desired physiological responses, while minimizing undesirable effects.
Nanowires have been shown to function as phototransistors with a high degree of sensitivity. Due to the small lateral dimensions (100's of nanometers to 10's of microns) and large surface-to-volume ratio of silicon (Si) nanowires, the large number of states at a Si surface can trap carriers at the surface equivalent to a gate bias, resulting in phototransistive behavior that leads to high sensitivity. This unique property of Si nanowires makes these devices attractive for photodetection from ultraviolet to the near infrared. Zhang, A., et al. (“Silicon Nanowire Detectors Showing Phototransistive Gain”, Applied Physics Letters, 2008, Vol. 93, 121110 (−1 to −3) have shown that etched planar and vertical Si nanowires function effectively with gains exceeding 35,000 under low intensity UV illumination, demonstrating their potential for low light detection. The vertical Si nanowires in particular are effective at overcoming low physical fill factor (FF) limitations due to their strong waveguiding effects, which cause a large fraction of the photon energy to be funneled into the nanowires.